CaseCase forfor RevisionRevision ofof NationalNationalPMTCTPMTCT ProtocolProtocol && InitiatingInitiating ARTARTinin DriedDried BloodBlood SpotSpot HIVHIV--11 DNADNApositivepositive InfantsInfants

By

Dr. Anil Kumar Gupta MD (Pediatrics)

Additional Project DirectorDelhi State AIDS Control Society

Govt. of Delhi, India

IntroductionIntroduction

•Perinatal transmission - 5.4% of total HIV infections

•Current Indian PMTCT Protocol –

(i) Single-dose Nevirapine (SdNVP) to MB pair

(ii) Maternal HAART if CD4≤ 350

(iii) Exclusive breast feeding in first 6 months orreplacement feeding if AFASS criteria is metreplacement feeding if AFASS criteria is met

• Early infant diagnosis by HIV-1 DNA PCR -rolled out in Dec 2011 with aim to start early ART inHIV positive infants.

•Aims & Objectives- To assess the effectiveness ofcurrent Indian PMTCT interventions and challenges inearly initiation of ART in EID-detected HIV-positivechildren.

Material MethodsMaterial Methods

•Study Population : 217 HIV-exposed infants

•All mothers were counseled & PMTCTinterventions received by MB pair were recorded

• The HIV-1 DNA PCR testThe HIV-1 DNA PCR test

•CPT was initiated.

• Follow-up up to 18 months

Case DefinitionsCase Definitions� (i) HIV +ve :DBS & WB DNA PCR testsreported positive or positive 18-month RHT;

� (ii) HIV –ve: Replacement fed Infants withnegative DBS results found asymptomatic infollow-up, or Breast Fed infants with negative DBSresults after 6 weeks of discontinuing BF, or aresults after 6 weeks of discontinuing BF, or anegative 18-month Rapid HIV antibodyTest;

� (iii) LTFU—DBS +ve who did not return forWB-test, or BF or mixed-fed infants with firstnegative DBS who did not return for repeat test.

� HIV positive infants /children wereinitiated ART as soon as possibleirrespective of their CD4 count .

Research Centre for Health Economics and Evaluation (ReCHEE)

•MB pairs were categorized into three groupsbased on compliance with PMTCT protocol:

(i) ‘fully compliant’ (MB pair received ARV prophylaxis,eligible Pregnant Woman received HAART and infantreceived SdNVP or infant was either EBF or RF in first6 months),

(ii) ‘partly compliant’ (either mother or baby or nonereceived ARV prophylaxis, no maternal HAART toreceived ARV prophylaxis, no maternal HAART toeligible Pregnant Woman but baby received SdNVP orinfant was either EBF or RF) and

(iii) non-compliant’ (no ARV prophylaxis to eithermother or infant, no maternal HAART to eligible PWor baby was MF).

Results

Age of testing

(i) 186 (86%) < 6 mths , 31 (14% ) > 6 months- < 18 months

(ii) 112 (52%) were tested at 6 wks

Very high rate of delivery by C/S (50%)

A quarter received breast feedingA quarter received breast feeding

About 5% were mixed fed

CPT was initiated in all

Compliance to PMTCT Protocol

(i) Fully compliant- 154 ( 71%)

(ii) Partly compliant- 55 (25.3%)

(iii) Non-compliant- 8 (3.7%)

EID cascade.

A.Status of ARV & MTCT rateNumber MTCT rate (%)

(a) Maternal CD4 > 350 167(i) MB pair received SdNVP 94 8.5(ii) Maternal AZT+3TC

& infant AZT 19 0.0(iii) NoARV prophylaxis 54 32.3

(b) Maternal CD4 ≤ 350 50

PMTCT Protocol Vs MTCT Rate

(b) Maternal CD4 ≤ 350 50(i) Life long HAART initiatedin pregnancy 41 0.0(ii) HAART not initiated 9 55.5

B.MTCT rate Vs Compliance to PMTCT protocol:

(a) Fully compliant -5.2%(b) Partly compliant -14.5%(c) Non-compliant - 25%

Research Centre for Health Economics and Evaluation (ReCHEE)

Risk of HIV in Breast Fed Infants

• BF infants were five times more likely toturn HIV positive because 15 / 69 (21%) breast fedinfants were mixed fed .• Mixed Fed children were 18.3 times athigher risk for HIV & 5/ 15 (33%) mixed fedinfants turned HIV positive.infants turned HIV positive.• Maternal ARV & Breast feeding(a) None of the 18 BF infants with maternal HAARTinitiated during pregnancy and continued during BFturned HIV positive, whereas(b) 5 of 9 (55.6%) BF infants born to motherseligible for but not given HAART during pregnancywere HIV positive

•Significant Delay in ART Initiation , only a third wereinitiatedART below the age of 6 months•A third of children developed OIs due to delay ininitiating ART•Majority of children initiated ART are currently stable on ART

DiscussionDiscussion

•Overall MTCT rate of 8.3% comparable withanother report from India [Paranjpe SM, et al, WJA2012].

•However, if subjects testing positive in DBS testwho were LTFU are included in the analysis, thewho were LTFU are included in the analysis, theoverall MTCT rate would be 19.8% (43 of 217 MBpairs).

•This indicates that current recommendationsare only half effective, considering the MTCT rateof 35% without any intervention [WHO 2010].

PerinatalPerinatal transmissiontransmission inin IndiaIndia isis muchmuchhigherhigher thanthan thatthat reportedreported inin developeddeveloped countriescountries..Why?Why?

(i) SdNVP regimen is still used in India despitethe availability of a better regimen .

(ii) Universal Coverage of HAART for PW withCD4 < 350 because 80% of perinataltransmissions occur in such PW women andtransmissions occur in such PW women andHAART can prevent > 3/4th of HIV infectionsin infants. In this study, however, 18% of HIV-positive PW with CD4 counts <=350 were notinitiated HAART during pregnancy. Half of infantsborn to such mothers developed HIV, and threemothers died within 6 months of the birth of theirchild.

Research Centre for Health Economics and Evaluation (ReCHEE)

PerinatalPerinatal transmissiontransmission inin IndiaIndia isis muchmuchhigherhigher thanthan thatthat reportedreported inin developeddevelopedcountriescountries forfor severalseveral reasonsreasons (contd(contd..))

(iii) the Indian recommendation of EBF notbeing followed as one-fifth of mothers gaveformula milk to their child in addition to BF on thepretext of inadequate milk output, thereby increasingpretext of inadequate milk output, thereby increasingrisk of HIV transmission.

Therefore, the WHO recommendation ofproviding ARV prophylaxis either to themother or to the child for the entire durationof BF may be the only way to prevent BFtransmission given India’s hidden MFpractices.

Challenges in EID Challenges in EID

•The primary aim of EID is to identify HIV-infectedchildren early so that treatment can be startedpromptly before signs/symptoms of HIV develop.

•However, only 50% of HIV-exposed infants weretested at 6 weeks of age, and the earliest age oftested at 6 weeks of age, and the earliest age ofinitiation of ART was 4 months. Consequently,one-third of HIV-positive children developed OIs.

•Therefore, an earlier EID at 4 weeks of age maybe need of the hour (Sherman et al)

• LongTurn AroundTimes of EID Lab

Early Initiation of ART after first Early Initiation of ART after first Positive Virological test result ?Positive Virological test result ?

•After a positive DBS test, a confirmatory WB teston a fresh specimen is required immediately.•However, in the present study, only 42% of infantspositive for HIV on DBS tests underwent a WB test;some died and others were LFU.some died and others were LFU.•Considering these losses and that the RocheAmplicor DNA PCR assay has 100% sensitivity and99.6% specificity, current National Policy needsmodification as per revised WHO guidelines that, ‘ifvirological test result is positive, ART may be startedwithout delay, at same time a second specimenshould be collected to verify initial positivevirological test result.

ChallengesChallenges inin InitiationInitiation ofof ARTART inin HIVHIVpositivepositive infantsinfants && childrenchildren

•In this study, only half of all HIV-infectedchildren were given ART, and the remaining wereLFU.

• Parent of few HIV positive children denied ART• Parent of few HIV positive children denied ARTas their infants had no symptoms

•Some NVP-exposed HIV-infected infants werestarted the NVP containing regimen despitenational guidelines for a Protease Inhibitor (PI)-regimen, highlighting the lack of coordination amongintegrated counseling and testing andART centers

Research Centre for Health Economics and Evaluation (ReCHEE)

Future PerspectivesFuture Perspectives•A large number (50%) of HIV-positive PW deliveredthrough cesarean section. Adopting the triple ARVPMTCT regimen of WHO will obviate unnecessary electivecesarean sections on HIV-infected PW.

•Also, one-fifth of HIV-exposed infants were born to•Also, one-fifth of HIV-exposed infants were born toHIV-serodiscordant couples. UNICEF hasrecommended lifelong triple ARV therapy to all HIV-infected PW irrespective of CD4 count (option B+),which will not only prevent MTCT but may alsoreduce HIV transmission to spouses.

•Resource-limited countries like ours should explore foradvantage of the emerging evidence

RecommendationsRecommendations•SdNVP regimen should be replaced by the newWHO PMTCT regimen (Option B), with the firstvirological test performed in all HIV exposed infants at 6weeks of age.

•Counseling should include information to•Counseling should include information tocaregivers about implications of DNA PCR testresults in terms of acceptance of early initiation ofART in children detected HIV positive, and so that

•Infants testing positive on DBS tests may begiven ART without delay and simultaneously a WBspecimen for confirmatory DNA PCR testingtaken to aid in the decision to continue ART.

Research Centre for Health Economics and Evaluation (ReCHEE)